目的探讨绝经后女性2型糖尿病(T2DM)患者Wnt信号通路中血清DKK1、β-catenin基因的表达及与骨代谢的关系。方法收集新疆石河子社区、医院病人中2型糖尿病(T2DM)与糖耐量正常(NGT)受试者各50例,记录其年龄、身高、体重等一般临床基线资料...目的探讨绝经后女性2型糖尿病(T2DM)患者Wnt信号通路中血清DKK1、β-catenin基因的表达及与骨代谢的关系。方法收集新疆石河子社区、医院病人中2型糖尿病(T2DM)与糖耐量正常(NGT)受试者各50例,记录其年龄、身高、体重等一般临床基线资料,全自动生化分析仪测定空腹血糖(FPG)、血钙(Ca)、血磷(P)等生化指标,高压液相色谱法测定糖化血红蛋白(HbA1c);双能X线(DXA)法测定腰椎及股骨骨密度;采用荧光定量反转录聚合酶链式反应法(qRT-PCR)检测DKK1基因和β-catenin基因表达水平并进行统计分析。结果①对绝经后女性NGT组和T2DM组年龄以及体质指数(BMI)进行统计分析,组间均无统计学差异(P>0.05),说明资料齐,具有可比性。②与NGT组相比,T2DM组糖代谢指标:空腹血糖(fasting plasma glucose,FPG)、果糖胺(froctosamine,FMN)、HbA1c水平增高(P<0.01);骨代谢指标:磷(P)水平增高(P<0.01)。③T2DM组股骨(femur)骨密度(bone mineral density,BMD)较NGT组显著降低(P<0.05)。④与NGT组相比,T2DM组外周血白细胞中DKK1基因表达水平为NGT组的5.99倍,β-catenin基因表达水平为NGT组的0.46倍。⑤β-catenin基因在绝经后女性T2DM组中的表达与P呈负相关关系且差异具有统计学意义(P<0.05)。⑥以骨代谢指标(Ca、P、ALP)为应变量,以DKK1基因和β-catenin基因为自变量,进行多元线性回归分析,在T2DM组中,β-catenin基因进入以P为应变量的回归方程:Y=1.445-0.287X。结论绝经后女性T2DM患者Wnt信号通路表达异常,DKK1基因的高表达可能抑制了其下游通路的转导,从而导致β-catenin基因的低表达,致使该人群BMD水平的下降,进而参与骨质疏松(OP)的发生发展。展开更多
目的探讨骨硬化蛋白和dkk1与2型糖尿病患者骨密度相关性。方法这项横断面研究包括190名患有2型糖尿病的住院患者。我们根据不同的BMD水平将患者分为三组(即正常骨密度组,骨量减少组和骨质疏松组),并测量血清中骨硬化蛋白、dkk1、25-羟...目的探讨骨硬化蛋白和dkk1与2型糖尿病患者骨密度相关性。方法这项横断面研究包括190名患有2型糖尿病的住院患者。我们根据不同的BMD水平将患者分为三组(即正常骨密度组,骨量减少组和骨质疏松组),并测量血清中骨硬化蛋白、dkk1、25-羟基维生素D 3(25OHD3)的水平,每组的骨转换标志物和其他生化数据。结果在骨质疏松症组中发现血清骨硬化蛋白和dkk1水平显著增加,即使分别考虑男性和女性群组。回归分析表明,在调整年龄、性别和25OHD3后,血清硬化蛋白水平与骨质减少和骨质疏松症存在独立相关。BMD与血清骨硬化蛋白和dkk1水平呈负相关,与25OHD3呈正相关。此外,年龄、糖化血红蛋白和血清骨硬化蛋白水平是1型前胶原氨基末端前肽(N-propeptide of type 1 collagen,P1NP)的预测因子,血清dkk1水平是1型胶原交联羧基末端肽(C-terminal crosslinking telopeptides of type 1 collagen,1CTP)的唯一预测因子。结论骨硬化蛋白和dkk1水平随着骨质疏松症2型糖尿病患者BMD的降低而增加。展开更多
Objective: To investigate the changes of oncogene Dickkopf 2 (DKK2) and sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) expression in bladder cancer lesions and their correlation with cancer cel...Objective: To investigate the changes of oncogene Dickkopf 2 (DKK2) and sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) expression in bladder cancer lesions and their correlation with cancer cell proliferation and invasion. Methods: The bladder cancer lesions and paracancerous lesions surgically removed in our hospital between March 2016 and March 2018 were collected, and kits were used to measure the mRNA expression levels of DKK2, SPOCK1, proliferation genes and invasion genes. Results: DKK2, hyperplasia suppressor gene (HSG), p16, cell adhesion molecule-1 (CADM1), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) and TIMP4 mRNA expression in bladder cancer lesions were significantly lower than those in paracancerous lesions while SPOCK1, β-catenin, CyclinD1, c-myc, Vimentin and matrix metalloproteinase 2 (MMP2) mRNA expression were significantly higher than those in paracancerous lesions;DKK2 was negatively correlated with β-catenin, CyclinD1, c-myc, Vimentin and MMP2, and positively correlated with HSG, p16, CADM1, TIMP2 and TIMP4;SPOCK1 was positively correlated with β-catenin, CyclinD1, c-myc, Vimentin and MMP2, and negatively correlated with HSG, p16, CADM1, TIMP2 and TIMP4. Conclusion: The low expression of oncogene DKK2 and the high expression of SPOCK1 in bladder cancer lesions are related to the changes of proliferation and invasion genes and may be involved in the growth of lesions.展开更多
Background:Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease,this study aimed to establish the efficacy of a tr...Background:Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease,this study aimed to establish the efficacy of a transient plasmid-based preconditioning strategy for boosting the capability of mesenchymal stromal cells(MSCs)for anti-inflammation/antioxidant defenses and paracrine actions in recipient hepatocytes.Methods:Human adipose mesenchymal stem cells(hADMSCs)were subjected to transfer,either with or without the nuclear factor erythroid 2-related factor 2(Nrf2)/Dickkopf1(DKK1)genes,followed by exposure to TNF-a/H2O2.Mouse models were subjected to acute chronic liver failure(ACLF)and subsequently injected with either transfected or untransfected MSCs.These hADMSCs and ACLF mouse models were used to investigate the interaction between Nrf2/DKK1 and the hepatocyte receptor cytoskeleton-associated protein 4(CKAP4).Results:Activation of Nrf2 and DKK1 enhanced the anti-stress capacity of MSCs in vitro.In a murine model of ACLF,transient co-overexpression of Nrf2 and DKK1 via plasmid transfection improved MSC resilience against inflammatory and oxidative assaults,boosted MSC transplantation efficacy,and promoted recipient liver regeneration due to a shift from the activation of the anti-regenerative IFN-c/STAT1 pathway to the pro-regenerative IL-6/STAT3 pathway in the liver.Importantly,the therapeutic benefits of MSC transplantation were nullified when the receptor CKAP4,which interacts with DKK1,was specifically removed from recipient hepatocytes.However,the removal of the another receptor low-density lipoprotein receptor-related protein 6(LRP6)had no impact on the effectiveness of MSC transplantation.Moreover,in long-term observations,no tumorigenicity was detected in mice following transplantation of transiently preconditioned MSCs.Conclusions:Co-stimulation with Nrf2/DKK1 safely improved the efficacy of human MSC-based therapies in murine models of ACLF through CKAP4-dependent paracrine mechanisms.展开更多
文摘目的探讨绝经后女性2型糖尿病(T2DM)患者Wnt信号通路中血清DKK1、β-catenin基因的表达及与骨代谢的关系。方法收集新疆石河子社区、医院病人中2型糖尿病(T2DM)与糖耐量正常(NGT)受试者各50例,记录其年龄、身高、体重等一般临床基线资料,全自动生化分析仪测定空腹血糖(FPG)、血钙(Ca)、血磷(P)等生化指标,高压液相色谱法测定糖化血红蛋白(HbA1c);双能X线(DXA)法测定腰椎及股骨骨密度;采用荧光定量反转录聚合酶链式反应法(qRT-PCR)检测DKK1基因和β-catenin基因表达水平并进行统计分析。结果①对绝经后女性NGT组和T2DM组年龄以及体质指数(BMI)进行统计分析,组间均无统计学差异(P>0.05),说明资料齐,具有可比性。②与NGT组相比,T2DM组糖代谢指标:空腹血糖(fasting plasma glucose,FPG)、果糖胺(froctosamine,FMN)、HbA1c水平增高(P<0.01);骨代谢指标:磷(P)水平增高(P<0.01)。③T2DM组股骨(femur)骨密度(bone mineral density,BMD)较NGT组显著降低(P<0.05)。④与NGT组相比,T2DM组外周血白细胞中DKK1基因表达水平为NGT组的5.99倍,β-catenin基因表达水平为NGT组的0.46倍。⑤β-catenin基因在绝经后女性T2DM组中的表达与P呈负相关关系且差异具有统计学意义(P<0.05)。⑥以骨代谢指标(Ca、P、ALP)为应变量,以DKK1基因和β-catenin基因为自变量,进行多元线性回归分析,在T2DM组中,β-catenin基因进入以P为应变量的回归方程:Y=1.445-0.287X。结论绝经后女性T2DM患者Wnt信号通路表达异常,DKK1基因的高表达可能抑制了其下游通路的转导,从而导致β-catenin基因的低表达,致使该人群BMD水平的下降,进而参与骨质疏松(OP)的发生发展。
文摘目的探讨骨硬化蛋白和dkk1与2型糖尿病患者骨密度相关性。方法这项横断面研究包括190名患有2型糖尿病的住院患者。我们根据不同的BMD水平将患者分为三组(即正常骨密度组,骨量减少组和骨质疏松组),并测量血清中骨硬化蛋白、dkk1、25-羟基维生素D 3(25OHD3)的水平,每组的骨转换标志物和其他生化数据。结果在骨质疏松症组中发现血清骨硬化蛋白和dkk1水平显著增加,即使分别考虑男性和女性群组。回归分析表明,在调整年龄、性别和25OHD3后,血清硬化蛋白水平与骨质减少和骨质疏松症存在独立相关。BMD与血清骨硬化蛋白和dkk1水平呈负相关,与25OHD3呈正相关。此外,年龄、糖化血红蛋白和血清骨硬化蛋白水平是1型前胶原氨基末端前肽(N-propeptide of type 1 collagen,P1NP)的预测因子,血清dkk1水平是1型胶原交联羧基末端肽(C-terminal crosslinking telopeptides of type 1 collagen,1CTP)的唯一预测因子。结论骨硬化蛋白和dkk1水平随着骨质疏松症2型糖尿病患者BMD的降低而增加。
文摘Objective: To investigate the changes of oncogene Dickkopf 2 (DKK2) and sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) expression in bladder cancer lesions and their correlation with cancer cell proliferation and invasion. Methods: The bladder cancer lesions and paracancerous lesions surgically removed in our hospital between March 2016 and March 2018 were collected, and kits were used to measure the mRNA expression levels of DKK2, SPOCK1, proliferation genes and invasion genes. Results: DKK2, hyperplasia suppressor gene (HSG), p16, cell adhesion molecule-1 (CADM1), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) and TIMP4 mRNA expression in bladder cancer lesions were significantly lower than those in paracancerous lesions while SPOCK1, β-catenin, CyclinD1, c-myc, Vimentin and matrix metalloproteinase 2 (MMP2) mRNA expression were significantly higher than those in paracancerous lesions;DKK2 was negatively correlated with β-catenin, CyclinD1, c-myc, Vimentin and MMP2, and positively correlated with HSG, p16, CADM1, TIMP2 and TIMP4;SPOCK1 was positively correlated with β-catenin, CyclinD1, c-myc, Vimentin and MMP2, and negatively correlated with HSG, p16, CADM1, TIMP2 and TIMP4. Conclusion: The low expression of oncogene DKK2 and the high expression of SPOCK1 in bladder cancer lesions are related to the changes of proliferation and invasion genes and may be involved in the growth of lesions.
基金funded by grants from the National Natural Science Foundation of China[nos 82122009,81970515,82170605,and 81873573]the Guangdong Natural Science Funds for Distinguished Young Scholar[no.2019B151502013]the Guangdong Basic and Applied Research Foundation[no.2021B1515120069].
文摘Background:Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease,this study aimed to establish the efficacy of a transient plasmid-based preconditioning strategy for boosting the capability of mesenchymal stromal cells(MSCs)for anti-inflammation/antioxidant defenses and paracrine actions in recipient hepatocytes.Methods:Human adipose mesenchymal stem cells(hADMSCs)were subjected to transfer,either with or without the nuclear factor erythroid 2-related factor 2(Nrf2)/Dickkopf1(DKK1)genes,followed by exposure to TNF-a/H2O2.Mouse models were subjected to acute chronic liver failure(ACLF)and subsequently injected with either transfected or untransfected MSCs.These hADMSCs and ACLF mouse models were used to investigate the interaction between Nrf2/DKK1 and the hepatocyte receptor cytoskeleton-associated protein 4(CKAP4).Results:Activation of Nrf2 and DKK1 enhanced the anti-stress capacity of MSCs in vitro.In a murine model of ACLF,transient co-overexpression of Nrf2 and DKK1 via plasmid transfection improved MSC resilience against inflammatory and oxidative assaults,boosted MSC transplantation efficacy,and promoted recipient liver regeneration due to a shift from the activation of the anti-regenerative IFN-c/STAT1 pathway to the pro-regenerative IL-6/STAT3 pathway in the liver.Importantly,the therapeutic benefits of MSC transplantation were nullified when the receptor CKAP4,which interacts with DKK1,was specifically removed from recipient hepatocytes.However,the removal of the another receptor low-density lipoprotein receptor-related protein 6(LRP6)had no impact on the effectiveness of MSC transplantation.Moreover,in long-term observations,no tumorigenicity was detected in mice following transplantation of transiently preconditioned MSCs.Conclusions:Co-stimulation with Nrf2/DKK1 safely improved the efficacy of human MSC-based therapies in murine models of ACLF through CKAP4-dependent paracrine mechanisms.
